As an evolutionary
biologist I love phylogenies. Or, I love phylogenies so I became an evolutionary
biologist. Except I did not always know what a phylogeny was. A phylogeny is
similar to a family tree except we usually have to infer who the ancestors
were. To do this, we collect and study present-day organisms and use the data
to reconstruct what happened millions of years ago. In the end we are left with
an illustration of relationships, a phylogeny, which gives us an idea of who is
more closely related to whom. Are beetles more closely related to ants or
cockroaches? Ants. Are pine trees more closely related to kelp or moss? Moss. In
fact, there is a huge push to understand what is called the Tree of Life
– a phylogeny that includes all the major extant (living) organismal lineages.
An updated version was recently published and did a nice job of putting humans in our place. We are not as big of a deal
as we like to think, evolutionarily speaking - we are merely a small nubbin on the twig of ‘Eukaryotes’.
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| Recently published phylogeny of the Tree of Life (Hug et al., 2016) |
Understanding phylogenetic relationships
gives us a foundation to test hypotheses and tease out answers about how our
world works. The information we retrieve tells us that birds are actually dinosaurs, neanderthals exchanged genes with humans, and that immune systems can evolve
under pressure from viruses and other pathogens.
That's where we are going today - using phylogenies
to unpack the evolutionary dynamics of one-up-man-ship between a virus and the
host immune system. The plan is to delve deep into stuff that will make you say,
wow. First, a little background. I am not going into great detail about Ebola
as this has been extensively covered.
Briefly, Ebola is a filamentous virus, categorized as a filovirus, which
infects humans (and other mammals) resulting in viral hemorrhagic fevers that
can be fatal. In addition to researching treatment and vaccine options for Ebola, scientists are conducting
research to understand how the virus ‘jumps’ from a non-human host to humans
(a.k.a a spillover event).
To do that, we first need to figure out what that non-human host is.
Based on data showing remnants of filoviruses in fruit-eating bats
and insect-eating bats,
many researchers are focusing on bats as a likely reservoir. Of course there
are many questions making this is an active area of research. One of those
questions, investigated by Ng et al. (2015),
is: how come bats do not seem susceptible to Ebola and other filoviruses? The
short, brief, and tractable answer of the Ng et al. study is that some bats
have a genetic mutation in the protein filoviruses use to bind to and infect
the bat’s cells. It would be like playing a game of Pac-Man where the ghosts
have gone wild and the only way Pac-Man can stay alive is by having a mutation
that prevents the ghosts from recognizing him. Did I just date myself? Or,
let’s try this analogy. Hackers recently found a way to generate ‘universal keys’ allowing them to break into cars with keyless entry systems.
This would be our virus hacker, breaking into cars using sophisticated
biochemical tactics. But, let’s say there is one type of car (the new Tesla
Model 3?) that has changed its keyless entry system so it is no longer
susceptible to hacking. The virus hacker tries its key against the lock but it
doesn’t work. Now, of course, people with the resistant car are more likely to keep
their cars in this hacking environment, and the desire to have this car spreads
and they become more and more frequent. Tough luck for the hacker.
And this is what Ng et al. (2015) found. The
mutation that prevents Ebola virus from attaching to the bat’s cells is under
positive selection, meaning that its frequency in the population increased
rapidly relative to other genes. When researchers find evidence of positive
selection it lends further support to the idea that something important is happening. Interestingly,
Ng et al. found that not all bat species had the mutation.
In walks the bat phylogeny. Bats are a diverse group of flying mammals with over 1200 species that
live in many different habitats all over the world.
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| Townsend's big-eared bat (Corynorhinus townsendii), a nice picture of a bat but not one included in the study by Ng et al. (Image Credit) |
If we want to understand disease dynamics,
and how and why some bats have the mutation and others don’t, we can use the
phylogeny as a forensic tool to reconstruct how resistance evolved. We can ask
questions like: are bats with the mutation close relatives? Did they inherit it
from an ancestor? Or, did the mutation evolve multiple times in different bat
species? And, due to the innate curiosity of humans, there are phylogenies for lots of different animal groups, including bats.
In 2007, Miller-Butterworth and colleagues
put together an impressive genetic data set (over 11,000 base pairs of DNA) to
essentially go back in time and figure out how different types of bats are
related to each other. It is important to point out here that our estimates of
phylogenetic relationships are just that, estimates. The reason is that any
given phylogeny is a hypothesis, our best estimate given the data available.
For a long time, biologists relied on morphological data to figure out who was
most closely related to whom. Evidence of close relationship was inferred if
two species shared a trait that was presumably inherited from a common
ancestor. But you can imagine how this might lead to spurious relationships.
Just because both bats and birds have wings, it doesn’t mean they are close
relatives. We know from studying the morphology underlying bird and bat wings
that these animals did not inherit wings from a common ancestor, they each
evolved them independently; thus, it would be a mistake to infer they are close
relatives because they both have wings. In the past few decades, researchers
have been able to rely more heavily on genetic data to infer relationships. And
while these data have their own set of problems, they provide an additional
perspective to consider alongside morphological data. As new technologies are
developed and our ability to accumulate more data improves, our phylogenies are
continuously updated and remain dynamic. This may frustrate many students in
introductory biology classes, but underscores the importance of understanding
the process and history of scientific data collection and hypothesis testing.
Back to bats. What Ng and colleagues found
when they combined their data with the bat phylogeny was that the mutation
preventing filovirus infection evolved once about 25 million years ago, and was
passed down to descendant lineages. The researchers interpreted these results
as evidence that bats have been evolving alongside filoviruses, and for much longer
than previously thought. But what do we know about hackers that we should be
thinking about here? They evolve too. Just because the Model 3 may be resistant
to hackers now, the hackers are not going to sit idle and find another means of
making a living. The hacker tactics will shift and evolve to overcome new
car-locking technology. And Ng et al. found evidence of this happening between bats and Ebola too. What they see is multiple mutations with a signature of positive selection, which they suggest results from counter-attacks by the virus. In other words, the virus sees the bat mutation and raises it a mutation of its own. It is an arms race. Between the virus and its host. Between the hacker and the car company. It is known as the Red Queen Hypothesis
(coined by Leigh Van Valen in 1973) and that is a story for another day.
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| “Now, HERE, you see, it takes all the running YOU can do, to keep in the same place.” (Lewis Carroll, Through the Looking Glass) |
P.S. There is a nice podcast on TWiEVO discussing the Ng et al. (2015) paper with some of the authors of the paper.
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